Isolation and structure of antagonists of chemokine receptor (CCR5)

Human CCR5 is a G-coupled receptor that binds to the envelope protein gp120 and CD4 and mediates the HIV-1 viral entry into the cells. The blockade of this binding by a small molecule receptor antagonist could lead to a new mode of action agent for HIV-1 and AIDS. Screening of natural product extracts led to the identification of anibamine (1), a novel pyridine quaternary alkaloid as a TFA salt, from Aniba sp.; ophiobolin C from fermentation extracts of fungi Mollisia sp.; and 19,20-epoxycytochalasin Q from Xylaria sp. Formation of the TFA salt of anibamine is plausibly an artifact of the isolation. The identity of the natural counterion is unknown. Anibamine-TFA competed for the binding of I-125-gp120 to human CCR5 with an IC50 Of 1 muM. Ophiobolin C and 19,20-epoxycytochalasin Q exhibited binding IC50 values of 40 and 60 muM, respectively.